Cladribine (3 brand names, 2 dosage forms, 2 routes)
Available dosage forms: INJECTABLE, TABLET.
Routes of administration: INJECTION, ORAL.
Brand Names
- CLADRIBINE
- LEUSTATIN
- MAVENCLAD
Indications and Usage
Cladribine is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, use of cladribine is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS [see Warnings and Precautions (5)].
Contraindications
Cladribine is contraindicated: in patients with current malignancy [see Warnings and Precautions (5.1)]. in pregnant women and in females and males of reproductive potential who do not plan to use effective contraception during cladribine dosing and for 6 months after the last dose in each treatment course for females and 14 weeks for males. May cause fetal harm [see Warnings and Precautions (5.2)and Use in Specific Populations (8.1, 8.3)] . in patients infected with the human immunodeficiency virus (HIV ) [see Warnings and Precautions (5.4)]. in patients with active chronic infections (e.g., hepatitis or tuberculosis) [see Warnings and Precautions (5.4)]. in patients with a history of hypersensitivity to cladribine [see Warnings and Precautions (5.8)]. in females intending to breastfeed on a cladribine treatment day and for 10 days after the last dose [see Use in Specific Populations (8.2)].
Adverse Reactions
The following serious adverse reactions and potential risks are discussed, or discussed in greater detail, in other sections of the labeling: Malignancies [see Warnings and Precautions (5.1)] Risk of Teratogenicity [see Warnings and Precautions (5.2)] Lymphopenia [see Warnings and Precautions (5.3)] Infections [see Warnings and Precautions (5.4)] Hematologic Toxicity [see Warnings and Precautions (5.5)] Graft-Versus-Host Disease With Blood Transfusion [see Warnings and Precautions (5.6)] Liver Injury [see Warnings and Precautions (5.7)] Hypersensitivity [see Warnings and Precautions (5.8)] Cardiac Failure [see Warnings and Precautions (5.9)]
Drug Interactions
Table 3 Drug Interactions with Cladribine 7.1 Immunomodulatory, Immunosuppressive, or Myelosuppressive Drugs Clinical Impact Concomitant use of cladribine with immunomodulatory, immunosuppressive, or myelosuppressive drugs may increase the risk of adverse reactions because of the additive effects on the immune system [see Warnings and Precautions (5.4)] . Prevention or Management Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short- term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of cladribine. 7.2 Interferon-Beta Clinical Impact Concomitant use of cladribine with interferon-beta did not change the exposure of cladribine to a clinically significant effect; however, lymphopenia risk may be increased [see Warnings and Precautions (5.3)]. Prevention or Management Concomitant use is not recommended. 7.3 Hematotoxic Drugs Clinical Impact Concomitant use of cladribine with hematotoxic drugs may increase the risk of adverse reactions because of the additive hematological effects [see Warnings and Precautions (5.5)]. Prevention or Management Monitor hematological parameters. 7.4 Antiviral and Antiretroviral Drugs Clinical Impact Compounds that require intracellular phosphorylation to become active (e.g., lamivudine, zalcitabine, ribavirin, stavudine, and zidovudine) could interfere with the intracellular phosphorylation and activity of cladribine. Prevention or Management Avoid concomitant use . 7.5 Potent ENT, CNT and BCRP Transporter Inhibitors Clinical Impact Cladribine is a substrate of breast cancer resistance protein (BCRP), equilibrative nucleoside (ENT1), and concentrative nucleoside (CNT3) transport proteins. The bioavailability, intracellular distribution, and renal elimination of cladribine may be
Mechanism of Action
The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes.
Overdosage
There is no experience with overdose of cladribine. Lymphopenia is known to be dose-dependent. Particularly close monitoring of hematological parameters is recommended in patients who have been exposed to an overdose of cladribine [see Warnings and Precautions (5.3, 5.5)]. There is no known specific antidote to an overdose of cladribine. Treatment consists of careful observation and initiation of appropriate supportive measures. Discontinuation of cladribine may need to be considered. Because of the rapid and extensive intracellular and tissue distribution, hemodialysis is unlikely to eliminate cladribine to a significant extent.